7368
M. Bingul et al. / Tetrahedron 70 (2014) 7363e7369
149.6 (aryl C) and 162.5 (CO2Me); HRMS (ESIþ): found m/z
288.0828, [MþNa]þ, C13H15NNaO5 requires 288.0842.
C, 60.7; H, 5.9; N, 5.4%; nmax (KBr): 3319, 2949, 1712, 1539, 1519,
1501, 1441, 1351, 1319, 1248, 1209, 1154, 1087, 999, 776, 751 cmꢁ1
lmax (MeOH): 293 nm (ε 37,620 cmꢁ1 ꢁ1), 248 (74,019), 203
(49,003); 1H NMR (300 MHz, CDCl3):
3.80, 3.93 and 3.96 (each 6H,
s, OMe), 4.74 (2H, s, bridging CH2), 6.56 (2H, s, H5), 7.28 (2H, d, J
2.6 Hz, H3) and 9.01 (2H, br s, NH), 13C NMR (CDCl3):
37.0
(bridging CH2); 55.5, 55.6 and 61.1 (OMe), 98.4 (C5), 106.9 (C3),
123.7, 126.2, 128.2, 143.6, 159.2, 164.0 (aryl C) and 175.2 (CO2Me);
HRMS (ESIþ): found m/z 505.1592, [MþNa]þ, C25H26N2NaO8 re-
quires 505.1581.
;
M
4.1.4.3. Methyl 6-hydroxymethyl-4,7-dimethoxyindole-2-
carboxylate (19). Dark yellow powder, yield: 89%; mp 166 ꢀC;
nmax (KBr): 3421, 3326, 1704, 1703, 1644, 1528, 1501, 1448, 1405,
d
d
1355, 1320, 1243, 1212, 1095, 1063, 1018, 1002, 774, 748 cmꢁ1
;
lmax
(MeOH): 281 nm (ε 21,430 cmꢁ1 Mꢁ1), 248 (42,638), 204 (44,583);
1H NMR (300 MHz, CDCl3):
3.87 (6H, s, OMe), 3.97 (3H, s, CO2Me),
d
4.21 (1H, br s, CH2OH), 4.69 (2H, d, J 4.6 Hz, CH2OH), 6.61 (1H, s, H5),
7.23 (1H, d, J 2.3 Hz, H3) and 9.04 (1H, br s, NH), 13C NMR (CDCl3):
d
52.7 and 56.4 (OMe), 61.9 (CH2OH), 105.9 (C5), 107.2 (C3), 121.8,
4.1.5.4. Dimethyl 4,40-methylenebis-(5,6-dimethoxy-1H-indole)-
2,20-dicarboxylate (28). White powder, yield: 61%; mp 192 ꢀC; nmax
(KBr): 3331, 2945, 1688, 1633, 1528, 1503, 1443, 1418, 1358, 1290,
123.1, 127.1, 129.7, 142.8, 146.1 (aryl C) and 162.4 (CO2Me); HRMS
(ESIþ): found m/z 288.0846, [MþNa]þ, C13H15NNaO5 requires
288.0842.
1252, 1149, 1092, 1009, 845, 823, 764, 547 cmꢁ1
;
lmax (MeOH):
ꢁ1), 207 (43,668); 1H NMR (300 MHz,
2.79, 2.98 and 3.08 (each 6H, s, OMe), 4.13 (2H, s, bridging
CH2), 5.85 (2H, s, H7), 6.06 (2H, s, H3) and 7.79 (2H, br s, NH); 13C
NMR (CDCl3): 21.4 (bridging CH2), 51.8, 56.0 and 56.2 (OMe), 93.6
318 nm (ε 25,743 cmꢁ1
CDCl3):
M
4.1.4.4. Methyl 7-hydroxymethyl-4,6-dimethoxyindole-2-
carboxylate (20). Dark yellow powder, yield: 86%; mp 198 ꢀC;
nmax (KBr): 3441, 3390, 1706, 1649, 1626, 1597, 1520, 1440, 1309,
d
d
1276, 1216, 1192, 1170, 1125, 1091, 990, 759, 749 cmꢁ1
;
lmax
(MeOH): 278 nm (ε 19,590 cmꢁ1 Mꢁ1), 245 (38,670), 203 (34,761);
1H NMR (300 MHz, CDCl3):
3.94, 3.96 and 3.97 (each 3H, s, OMe),
(C7), 102.0 (C3), 121.5, 121.8, 123.5, 131.5, 145.7, 150.4 (aryl C) and
163.1 (CO2Me); HRMS (ESIþ): found m/z 505.1609, [MþNa]þ,
d
C25H26N2NaO8 requires 505.1581.
4.23 (1H, br s, CH2OH), 4.80 (2H, s, CH2OH), 6.48 (1H, s, H5), 7.12
(1H, d, J 1.9 Hz, H3) and 11.15 (1H, br s, NH); 13C NMR (CDCl3):
4.1.6. General procedure for the preparation of unsymmetrical diin-
dolylmethanes (29e30). A mixture of indole-2-carboxylate
(100 mg, 0.40 mmol) and hydroxymethylindole-2-carboxylate
(112 mg, 0.42 mmol) in glacial acetic acid (4.0 mL) was stirred at
room temperature for 2 h. The resulting precipitate was filtered,
washed successively with glacial acetic acid, water, and then sat-
urated sodium bicarbonate solution. The resulting solid was dried
and purified by flash chromatography using dichloromethane as
eluent to afford the title compound.
d
52.0, 53.8 and 55.7 (OMe), 57.2 (CH2OH), 89.7 (C5), 106.0 (C3),
113.5, 114.9, 125.6, 138.7, 153.9, 156.2 (aryl C) and 161.8 (CO2Me);
HRMS (ESIþ): found m/z 288.0833, [MþNa]þ, C13H15NNaO5 re-
quires 288.0842.
4.1.5. General procedure for the preparation of symmetrical diindo-
lylmethanes (25e28). A solution of hydroxymethylindole-2-
carboxylate (100 mg, 0.38 mmol) in glacial acetic acid (4.0 mL)
was stirred at room temperature for 3 days. The resulting pre-
cipitate was filtered, washed twice with acetic acid (2 mL) and then
with water. Upon drying, the residue was purified by flash chro-
matography using dichloromethane as eluent to afford the title
compound.
4.1.6.1. Methyl 7-((5,6-dimethoxy-2-methoxycarbonyl-1H-indol-
4-yl)methyl)-4,6-dimethoxy-1H-indole-2-carboxylate
(29). White
powder, yield: 74%; mp 284 ꢀC; found: C, 61.1; H, 5.6; N, 5.1. Anal.
Calcd for C25H26N2O8.0.1CH3OH; C, 60.7; H, 5.9; N, 5.4%; nmax (KBr):
3346, 1722, 1623, 1599, 1543, 1524, 1268, 1203, 1123, 1091, 1001,
4.1.5.1. Dimethyl 7,70-methylenebis-(4,6-dimethoxy-1H-indole)-
2,20-dicarboxylate (25). White powder, yield: 62%; mp 296 ꢀC; nmax
(KBr): 3345, 1721, 1622, 1598, 1543, 1524, 1462, 1461, 1438, 1348,
764 cmꢁ1
;
lmax (MeOH): 306 nm (ε 20,600 cmꢁ1
M
ꢁ1), 245
(25,570), 204 (36,110); 1H NMR (300 MHz, CDCl3):
d 3.84, 3.85 and
4.18 (each 6H, s, OMe), 4.19 (2H, s, bridging CH2), 6.27 (2H, s, H50
and H7), 7.12 (2H, d, J 2.6 Hz, H3 and H30) and 10.29 (2H, br s, NH);
1300, 1268, 1203, 1176, 1123, 1001, 993, 764 cmꢁ1
;
lmax (MeOH):
ꢁ1), 207 (46,580); 1H NMR (300 MHz,
3.84, 3.86 and 4.18 (each 6H, s, OMe), 4.20 (2H, s, bridging
CH2), 6.26 (2H, s, H5), 7.11 (2H, d, J 2.2 Hz, H3) and 10.30 (2H, br s,
NH); 13C NMR (CDCl3):
34.7 (bridging CH2), 55.4, 59.2 and 60.8
318 nm (ε 27,460 cmꢁ1
CDCl3):
M
13C NMR (CDCl3):
d 31.3 (bridging CH2), 52.1, 55.9 and 57.5 (OMe),
d
88.8 (C50), 104.0 (C7), 107.0 (C3), 114.5, 126.0, 139.1, 154.1, 156.1,
162.9 (aryl C) and 173.1 (CO2Me); HRMS (ESIþ): found m/z 505.1583,
[MþNa]þ, C25H26N2NaO8 requires 505.1581.
d
(OMe), 92.1 (C5), 107.3 (C3), 110.4, 117.8, 129.3, 142.4, 157.5, 166.2
(aryl C) and 173.08 (CO2Me); HRMS (ESIþ): found m/z 505.1576,
[MþNa]þ, C25H26N2NaO8 requires 505.1581.
4.1.6.2. Methyl 6-((5,6-dimethoxy-2-methoxycarbonyl-1H-indol-
4-yl)methyl)-4,7-dimethoxy-1H-indole-2-carboxylate
(30). White
powder, yield: 77%; mp 220 ꢀC; found: C, 49.1; H, 4.7; N, 4.2. Anal.
Calcd for C25H26N2O8.0.02CH2Cl2; C, 49.6; H, 4.6; N, 4.3%; nmax
(KBr): 3323, 2949, 1701, 1538, 1502, 1484, 1445, 1349, 1319, 1248,
4.1.5.2. Dimethyl 7,70-methylenebis-(4,5-dimethoxy-1H-indole)-
2,20-dicarboxylate (26). White powder, yield: 67%; mp 296 ꢀC; nmax
(KBr): 3315, 1756, 1610, 1543, 1488, 1456, 1399, 1376, 1366, 1310,
1209, 1158, 1088, 1001, 982, 775, 474 cmꢁ1
;
lmax (MeOH): 295 nm (ε
ꢁ1), 245 (34,463), 203 (49,121); 1H NMR (300 MHz,
3.74, 3.92 and 4.02 (each 6H, s, OMe), 4.54 (2H, s, bridging
CH2), 6.36 (1H, s, H7), 6.57 (1H, s, H50), 6.74 (1H, s, H30), 7.03 (1H, s,
1287, 1230, 1140, 1131, 1108, 1062, 999, 778, 660 cmꢁ1
;
lmax
ꢁ1), 234 (72,060), 204
d 3.81, 3.93 and 4.01 (each
88,195 cmꢁ1
CDCl3):
M
(MeOH): 295 nm (ε 44,520 cmꢁ1
M
d
(109,690); 1H NMR (300 MHz, CDCl3):
6H, s, OMe), 4.17 (2H, s, bridging CH2), 6.44 (2H, s, H6), 7.22 (2H, d,
H3) and 8.98 (2H, br s, NH); 13C NMR (CDCl3):
d 30.3 (bridging CH2),
J 2.2 Hz, H3) and 9.26 (2H, br s, NH); 13C NMR (CDCl3):
d
29.2
51.5, 55.4 and 55.8 (OMe), 93.2 (C50), 104.2 (C7), 106.5 (C30), 106.7
(C3), 121.0, 122.8, 124.1, 131.2, 145.4, 164.8 (aryl C) and 174.5
(CO2Me); HRMS (ESIþ): found m/z 505.1594, [MþNa]þ,
(bridging CH2), 56.7, 59.1 and 61.9 (OMe), 94.6 (C5), 105.1 (C3),
111.8, 116.0, 132.3, 146.2, 159.9, 161.4 (aryl C) and 175.2 (CO2Me);
HRMS (ESIþ): found m/z 505.1567, [MþNa]þ, C25H26N2NaO8 re-
quires 505.1581.
C25H26N2NaO8 requires 505.1581.
Acknowledgements
4.1.5.3. Dimethyl 6,60-methylenebis-(4,7-dimethoxy-1H-indole)-
2,20-dicarboxylate (27). White powder, yield: 59%; mp 196 ꢀC;
found: C, 60.6; H, 5.6; N, 5.5. Anal. Calcd for C25H26N2O8.0.1CH3OH;
We thank the University of New South Wales and the Turkish
Government for their financial support.